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Herein, this study investigated in silico the drug\u2010likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant\u2010like potential of RA in the lipopolysaccharide (LPS)\u2010induced depression model. RA (MW\u00a0=\u00a0360.31\u2009g\/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters. Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator\u2010activated receptor (PPAR) and the cannabinoid receptors CB\n                    <jats:sub>1<\/jats:sub>\n                    and CB\n                    <jats:sub>2<\/jats:sub>\n                    . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant\u2010like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB\n                    <jats:sub>1<\/jats:sub>\n                    , CB\n                    <jats:sub>2<\/jats:sub>\n                    , and PPAR\u2010\u03b3 receptors significantly blocked the antidepressant\u2010like effect of RA. Altogether, our findings suggest that cannabinoid receptors\/PPAR\u2010\u03b3 signaling pathways are involved with the antidepressant\u2010like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7318","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T08:31:25Z","timestamp":1635409885000},"page":"6974-6989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Antidepressant\u2010like effect of rosmarinic acid during\n                    <scp>LPS<\/scp>\n                    \u2010induced neuroinflammatory model: The potential role of cannabinoid receptors\/\n                    <scp>PPAR<\/scp>\n                    \u2010\u03b3 signaling pathway"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4710-6799","authenticated-orcid":false,"given":"Alexandre Augusto Barros","family":"Lataliza","sequence":"first","affiliation":[{"name":"Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Ararangu\u00e1 Universidade Federal de Santa Catarina  Ararangu\u00e1 Brazil"},{"name":"Post\u2010Graduate Program of Neuroscience, Center of Biological Sciences Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-2527","authenticated-orcid":false,"given":"Pollyana Mendon\u00e7a","family":"de Assis","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Health Sciences (NUPICS), Faculty of Pharmacy Universidade Federal de Juiz de Fora  Juiz de Fora Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa","family":"da Rocha Laurindo","sequence":"additional","affiliation":[{"name":"Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Ararangu\u00e1 Universidade Federal de Santa Catarina  Ararangu\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0682-3019","authenticated-orcid":false,"given":"Elaine Cristina Dalazen","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Ararangu\u00e1 Universidade Federal de Santa Catarina  Ararangu\u00e1 Brazil"},{"name":"Post\u2010Graduate Program of Neuroscience, Center of Biological Sciences Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5271-1048","authenticated-orcid":false,"given":"N\u00e1dia Rezende Barbosa","family":"Raposo","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Health Sciences (NUPICS), Faculty of Pharmacy Universidade Federal de Juiz de Fora  Juiz de Fora Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6938-2161","authenticated-orcid":false,"given":"Rafael Cypriano","family":"Dutra","sequence":"additional","affiliation":[{"name":"Laboratory of Autoimmunity and Immunopharmacology, Department of Health Sciences, Campus Ararangu\u00e1 Universidade Federal de Santa Catarina  Ararangu\u00e1 Brazil"},{"name":"Post\u2010Graduate Program of Neuroscience, Center of Biological Sciences Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"},{"name":"Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences Universidade Federal de Santa Catarina  Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","first-page":"217","article-title":"Activation of endocannabinoid transmission induces antidepressant\u2010like effects in rats","volume":"59","author":"Adamczyk P.","year":"2008","journal-title":"Journal of Physiology and Pharmacology"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00117"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x17666191001142934"},{"key":"e_1_2_9_6_1","unstructured":"Bains N. &Abdijadid S.(2020).Major depressive disorder. 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